Exosome-mediated neuroprotection in vascular dementia: Mechanisms, molecular pathways, and therapeutic prospects

Exosomes, a specialized class of extracellular vesicles, exhibit significant therapeutic potential for neurological disorders. In particular for vascular dementia (VaD), the second most common form of dementia. VaD is characterized by cognitive and behavioral impairments, often linked to hippocampal damage resulting from its vulnerable vascular structure, which disrupts memory formation and retrieval. Secreted by various cell types within the central nervous system, exosomes mediate intercellular communication by transporting bioactive molecules. Growing evidence indicates that exosomes enhance synaptic plasticity, modulate neuroinflammation, inhibit apoptosis, and promote angiogenesis, supporting their therapeutic potential in VaD. Given the urgent need for effective treatments and the unique ability of exosomes to cross the blood-brain barrier (BBB) and deliver multi-targeted therapies, research in this field is critically important. It offers a viable pathway toward the development of disease-modifying interventions for a condition that is currently managed primarily through symptomatic treatment. This review summarizes current knowledge on the function of exosomes in the central nervous system, examines recent advances in exosome-based strategies for VaD, and discusses ongoing challenges and future directions for their clinical translation. • Exosomes enhance angiogenesis and strengthen neurovascular integrity in VaD. • Neuron- and glia-derived exosomes coordinate axonal growth and synaptic remodeling. • Stem cell-derived exosomes reduce Aβ, tau, and oxidative stress in preclinical models. • Plasma exosomal proteins offer promising biomarkers for cognitive impairment.